DE2711686B2 - Process for the preparation of isobutyramides - Google Patents

Description

The synthesis preferably begins with p-fluoro or p-bromophenol, which is converted into the sodium phenolate (I) Reaction with sodium in ethanol solution is transferred. The ethanol is then added by adding a Excess of toluene and subsequent distillation of the azeotrope replaced by toluene.

The N-cyanoalkyl-a-bromo-isobutyramide is added to the solution in toluene of formula (II), and then the reaction mixture is preferably during 6 to Heated under reflux for 15 hours.

The compounds prepared by the process according to the invention are pharmacologically active and show hypolipemic, hypotriglyceridemic, and hypocholesterolemic activity.

The following examples illustrate the invention.

example 1
N-cyanoethyl-p-chlorophenoxy-isobutyramide

3 l of ethanol, 60 g of sodium and 250 g of p-chlorophenol (1.944 mol) are placed in a 25 l reactor equipped with cooling and stirring devices. After stirring for one hour, 2 l of toluene are added and the ethanol / toluene azeotrope is removed by distillation. Another 21 toluene are added. Then 425 g of N-cyanoethyl - \ - bromoisobutyramide (1.944 mol) are added.

The reaction mixture is refluxed for K) h. Then 2 l of toluene are distilled off. That resulting mixture is treated with water; a precipitate is obtained. This is filtered off, washed with water and acidified with HCl until neutral. He is dried and off Diisopropyl ether crystallizes.

Are thus obtained 348 g (yield 67%) of a white crystalline product, mp 71 ⁰ C. The composition of the product corresponds to the formula C ₁₃ H ₁₅ CIOaN ₂ (molecular weight 266.72). The compound is insoluble in water, but soluble in most common organic solvents.

ίο B e i s ρ i e 1 2

N-cyanoethyl-p-fluorophenoxy-isobutyramide

The procedure of Example I is repeated except that the p -chlorophenol is through is ρ-fluorophenol that is replaced after treatment with sodium with N-cyanoethyl-A-bromoisobutyramide is implemented.

A white, crystalline product, melting point 75 ° C., is obtained in a yield of 67%. The analysis shows good agreement with the formula CnH ₁₅ FNiO-. (Molecular weight 250.2).

Example 3
N-cyanobutyl-p-chlorophenoxy-isobutyramide

The procedure of Example I is repeated with the exception that N-cyanoethyl-. \ - bromo-isobutyramide is replaced with N-cyanobutyl-.n-bromo-isobutyramide. The yield is 87% of a white, crystalline product, mp 88 ° C. The analysis shows good agreement with the formula C ₁₅ H ₁₉ CIN ₂ O ₂ .

Claims (1)

1 2 Claim:
Process for the preparation of isobutyramides of the general formula CH, R'— Z ^ VO — C — CO — NH— (CH ₂ J _n -CN CH, in which R ^{1 is} a fluorine or chlorine atom and η is an integer from 2 to 4, characterized in that a sodium phenolate of the general formula 1 -ONa (1) in a manner known per se with an N-cyanoalkyl-A-bromo-isobulyramide of the general formula II CH,
Br-C-CONH- (CH-O _n -CN (II) CH,
where R ¹ and η have the meanings given above, in a non-polar solvent. The invention relates to a process for the preparation of isobutyramides of the general FonrH CH, R '- / ~~ \ —O — C — CO —NH- (CH ₂ ), - CN CH, in which R ^{1 is} a fluorine or chlorine atom and n is an integer from 2 to 4 by the action of the corresponding substitution number. ten sodium phenolate of the general formula I. The above compounds are inventively ^R1 \ / - ^{QNa (l)} in a non-polar solvent to an N-cyanoalkyl-A-bromo-isobulyramide of the general formula II CH, Br — C-CONH- (CH ₂ ) ,, - CN (II) CH., where R 'and /? the meanings given above easily by reacting n-bromo-isobutyrylehlorid own, produced in a known manner. t> o and the appropriate omega-aminonitrile accordingly The N-cyanoalkyl-s-bromo-isobutyramide (II) can be obtained from the following reaction scheme: CH ₃ CH, I 'I Br-C-COCI + H ₂ N- (CHO _n -CN - Br-C-CONH (CH ₂ J _n CN I "I CH, CH,